A common blood
protein is found to bind to the agents
that cause BSE and vCJD, raising
hopes of tests and possibly cures.

The first natural molecule that
binds to the deformed
prions that cause variant CJD and BSE has been
found. The identification
of the blood protein, by a Swiss team,
may explain why prions have
such devastating effects on the
brain.

It
could also lead to new tests for the diseases which
can be conducted on
living people. It could make it possible to remove
prions from donated
blood destined for transfusions. And further in the
future, it might
eventually lead to the first treatments. In diseases such
as vCJD, BSE
and scrapie, a protein called PrP becomes deformed. It then
deforms
other PrP proteins, in a chain reaction.

Now a team led by Adriano
Aguzzi of the University Hospital
of Zurich has discovered that
plasminogen, a common protein in blood,
binds strongly to the
deformed prions that cause scrapie in mice and vCJD
in humans - but not
to normal PrP. "We were very surprised,"
Aguzzi says.

Clean
blood

There are growing fears that vCJD could be transmitted
by
contaminated blood products. Already, nearly a dozen countries have
banned donations from people who have lived in Britain.

The fact that a
common blood protein binds to deformed
prions makes it more likely that
blood could be infectious.

It might be possible to exploit plasminogen's selective
binding abilities to remove prions from the blood plasma used for
transfusions.
Aguzzi's lab is testing modified versions of plasminogen
to try to find
one that binds to prions even more strongly than the
natural molecule.

Prion test

In the meantime, says Aguzzi,
the discovery might help
researchers develop faster and more accurate
tests for prion diseases.

"We are interested in looking at this," says
Bruno Oesch of the Swiss firm Prionics, which makes a widely used test
for BSE. The finding could also help the search for a test that can be
used on living subjects. At the moment, prion diseases can only be
diagnosed
with certainty after death.

Martin Fischer, the lead author
of the new study, has
already been given funding by the Consortium for
Plasma Science to develop
a plasminogen-based test. The consortium
involves companies that make
blood products,such as Bayer, Aventis
Behring and Baxter Hyland Immuno.

Brain
damage

The damage seen in diseases such as vCJD cannot be
caused
simply by abnormal prions accumulating. The prions must
interact
with other molecules. "But no natural molecule had ever
been found
which binds to disease-causing prions, but not the normal
form," Aguzzi
says.

The ability of prions to selectively bind to plasminogen
might explain why they wreak havoc in the brain. Plasminogen is the
inactive
form of plasmin, a powerful enzyme that dissolves proteins. In
the brain,
plasmin is thought to allow synapses to remodel themselves,
a crucial process
for thought and memory.

What's really exciting, says
Aguzzi, is that Carlos Dotti
and his colleagues at the European
Molecular Biology Laboratory in Heidelberg
have found that on nerve
cells, the molecules that help turn plasminogen
into plasmin are
located on the same specialised patches of membrane as
normal
PrP.

Aguzzi thinks that prions might bind to nearby plasminogen
and
so interfere with its vital role in nerve function. He hopes to test
this theory by seeing whether mice engineered to lack plasminogen, or its
various activators, are immune to scrapie.

If prions do their damage by
binding to plasminogen,
it might be possible to find drugs that block
this. The team is already
investigating whether prions increase or
decrease plasminogen's conversion
to plasmin, and whether plasmin
destroys prions.

More at: Nature (vol 408, p 479)

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